American Journal of Psychiatry
March 17, 2021
R. Mcintyre, J. Rosenblat, C. Nemeroff et al.
694 citations
Ketamine and esketamine are the first non-monoamine-based antidepressants with rapid-onset efficacy for adults with treatment-resistant depression, offering hope to those who do not recover fully with standard antidepressants. However, concerns remain about their safety, tolerability, and appropriate placement in treatment algorithms. An international group of mood disorder experts synthesizes evidence on efficacy, safety, and tolerability, and provides guidance for clinical implementation, including practice parameters at point of care. Areas of consensus and future research directions are discussed.
Frontiers in Psychiatry
August 4, 2025
Fernando Mora, J. Ramos-Quiroga, Enrique Baca-García et al.
5 citations
Treatment-resistant depression (TRD) occurs when a patient fails to respond to at least two adequate antidepressant trials, and it imposes a greater social and economic burden than non-resistant depression. A committee of ten Spanish psychiatrists reviewed recent literature and developed consensus statements on TRD definitions, clinical response criteria, and the role of intranasal esketamine, which improves neuroplasticity and synaptogenesis. They highlighted therapeutic inertia—its causes and consequences—and produced a treatment algorithm that includes specific response evaluation steps to avoid inertia and ensure adequate treatment. This is the first Spanish consensus on theoretical aspects of TRD and intranasal esketamine's place in therapy.
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
A single day of treatment with an inhaled synthetic formulation of mebufotenin (GH001) significantly reduced depression symptoms in adults with treatment-resistant depression compared to placebo. In a randomized, double-blind trial of 81 patients, those receiving up to three escalating doses of GH001 showed an average 15.5-point greater improvement on the Montgomery-Åsberg Depression Rating Scale by day 8 than those on placebo. Remission rates were 57.5% for GH001 and 0% for placebo. No severe or serious adverse events occurred. The findings suggest GH001 may be a rapid-acting, well-tolerated treatment option for treatment-resistant depression.
European Neuropsychopharmacology
June 1, 2019
M. Bioque, S. Mas, M. Costanzo et al.
A specific genetic variation in the endocannabinoid system interacts with cannabis use to sharply increase the risk of a first episode of psychosis. Carrying two copies of the T allele of the FAAH rs2295633 gene variant, combined with cannabis use, made the probability of a first psychotic episode ten times higher compared to cannabis users without that genotype. No such increased risk appeared in non-users. The study also found that carriers of this genotype who used cannabis were more often treated with high-potency antipsychotics. The findings are preliminary and need replication.